This study is a randomized, double-blind, placebo-controlled, parallel-group trial comparing the effects of pioglitazone versus placebo in 50 patients with symptomatic (not well controlled or poorly controlled) allergic asthma and reversible airflow obstruction requiring EPR-3 Step 5 therapy (high dose inhaled corticosteroids with or without long-acting beta 2-agonists). The primary objective is to assess whether pioglitazone hydrochloride can improve airflow obstruction as measured by the post-bronchodilator FEV1. The secondary objectives are to assess the efficacy of pioglitazone hydrochloride on indices of airway inflammation, airflow obstruction, airway hyperreactivity, and asthma symptoms. We will screen up to 150 subjects to obtain 50 completed studies. Study participants must be between the ages of 18 and 75 and can be male or female. Patients will be counseled regarding alternative treatment options. Patients will be screened to assess whether they meet the inclusion and exclusion criteria. The following studies will be performed: history and physical examination, pulmonary function tests with methacholine bronchoprovocation challenge or responsiveness to inhaled beta 2-agonist, allergy skin testing, a chest x-ray, electrocardiogram, blood tests, asthma quality of life evaluation, asthma control score, cardiac echocardiogram, a DEXA bone scan and exhaled nitric oxide. Patients who fulfill the inclusion and exclusion criteria will be invited to participate in the study. The study will be divided into 3 phases;a 4-week run-in phase, a 10-week treatment phase, and a 4-week follow-up phase. All study visits will be performed on an outpatient basis. We anticipate 2 outpatient visits will be required to complete the screening assessment. Therefore, the study will include 9 outpatient visits. Patients enrolled in the study will continue to utilize their primary health care provider for their routine and emergent asthma care. Phase I Run-in Phase: Prior to being randomized to receive pioglitazone or placebo, patients will participate in a 4-week run-in phase, during which time baseline symptoms will be documented. Evaluations will be performed identical to those in the randomization phase. Patients must be free of respiratory tract infections and have stable asthma during the run-in period. Study subjects must also comply with home monitoring of asthma symptoms and peak expiratory flow during the run-in period to be eligible to proceed to the treatment phase. Study subjects who are unable to monitor daily asthma symptoms and peak expiratory flow rates will not be randomized to receive pioglitazone or placebo. At the completion of the run-in phase, patients will undergo pulmonary function testing with bronchodilator response, which is the primary end-point of the study. Patients will also undergo a sputum induction to assess indices of airway inflammation. Subjects will inhale 3% nebulized sterile saline for 12 minutes from an ultrasonic nebulizer, breathing normally, with a deep breath taken once a minute. Subjects will be instructed to stop every 4 minutes at which point they will be instructed to attempt to produce a sputum sample. Lung function will be monitored at 4, 8, and 12 minutes. Subjects who cannot produce an adequate sputum sample will continue in the study but will be excluded from the sputum analysis arm. Phase II - Treatment Phase: Patients will be randomized by the NIH Clinical Center pharmacy to receive either pioglitazone or a placebo that will match the active treatment. Patients will receive 30 mg daily of pioglitazone or placebo for the first 2 weeks of the study and then be escalated to 45 mg daily of pioglitazone or placebo for weeks 3 through 10. Patients will be monitored as outpatients on a biweekly basis for weeks 0 - 10 (+/- 4 days). Studies to be performed at each visit will include: history and physical examination, blood draw (CBC, electrolytes, LFTs, IgE, CPK, BNP, HbA1c, research blood), spirometry (pre- and post-bronchodilator), weight and body mass index, asthma control score, asthma quality of life score, and measurement of exhaled nitric oxide. Patients will keep a log at home of their asthma symptom score, inhaled beta-agonist use, and need for unscheduled medical care for asthma symptoms (urgent physician or emergency department visit, hospitalization). The daily morning and evening PEF and FEV1 will be recorded electronically. Study participants will be provided with an electronic peak flow meter for home monitoring of PEF and FEV1. At the completion of 10 weeks of therapy, patients will undergo repeat pulmonary function testing, methacholine bronchoprovocation challenge testing and induced sputum induction and analysis. Study participants will also undergo a repeat DEXA bone scan to assess the effects of pioglitazone treatment on bone density. If study participants are found to have developed osteopenia or osteoporosis, medically indicated treatment with calcium supplementation, Vitamin D, and bisphosphonate therapy will be instituted and a repeat DEXA bone scan performed in 12 months. Phase III Follow-up Evaluation Phase: Patients will undergo a follow-up evaluation, as described for phase II, at 4 weeks after the completion of the treatment phase for follow-up evaluation (week 14). This study was approved by the NHLBI IRB on 12/18/07 and there have been no enrollments to date.